Researchers have linked a specific type of body fat to the abnormal proteins in the brain that characterize Alzheimer’s disease, up to 20 years before the first symptoms of dementia appear, according to a study presented today at the annual meeting of the Radiological Society of North America (RSNA). The researchers emphasized that lifestyle changes aimed at reducing this fat could influence the development of Alzheimer’s disease.
This crucial result was discovered because we investigated the pathology of Alzheimer’s disease already in middle age, in the 1940s and 1950s, when the pathology of the disease is still in its earliest stages and possible changes such as weight loss and the reduction of visceral fat are more effective as a means. to prevent or delay the onset of the disease.”
Mahsa Dolatshahi, MD, MPH, lead study author, postdoctoral research associate at the Mallinckrodt Institute of Radiology (MIR) at Washington University School of Medicine in St. Louis, Missouri
According to the Alzheimer’s Association, an estimated 6.9 million Americans age 65 and older suffer from Alzheimer’s disease. The association estimates that this number could grow to 13 million by 2050, barring the development of medical breakthroughs to prevent or cure the disease.
For the study, the researchers focused on the link between modifiable lifestyle-related factors, such as obesity, body fat distribution and metabolic aspects, and the pathology of Alzheimer’s disease.
A total of 80 cognitively normal middle-aged individuals (mean age: 49.4 years, women: 62.5%) were included in the study. About 57.5% of participants were obese and the average body mass index (BMI) of participants was 32.31. The participants underwent positron emission tomography (PET), body MRI and metabolic assessment (glucose and insulin measurements), as well as a lipid (cholesterol) panel. MRI scans of the abdomen were performed to measure the volume of subcutaneous fat (the fat under the skin) and visceral fat (deeply hidden fat around the organs).
“We examined the association of BMI, visceral fat, subcutaneous fat, liver fat fraction, thigh fat and muscle, as well as insulin resistance and HDL (good cholesterol), with amyloid and tau deposition in Alzheimer’s disease,” said Dr. Dolatshahi, member of the Raji Lab of MIR’s Neuroimaging Labs Research Center.
Scans of the thigh muscles were used to measure muscle and fat volume. The pathology of Alzheimer’s disease was measured using PET scans with tracers that bind to amyloid plaques and tau tangles that build up in the brains of people with Alzheimer’s disease.
The findings showed that higher levels of visceral fat were associated with an increase in amyloid, which accounts for 77% of the effect of a high BMI on amyloid accumulation. Other types of fat could not explain obesity-related increased Alzheimer’s disease.
“Our study showed that higher visceral fat content was associated with higher PET levels of the two hallmark pathological proteins of Alzheimer’s disease: amyloid and tau,” said Dr. Dolatshahi. “To our knowledge, our study is the only one to demonstrate these findings in middle age, when our participants are decades away from developing the earliest symptoms of the dementia that results from Alzheimer’s disease.”
The study also showed that higher insulin resistance and lower HDL were associated with high amyloid levels in the brain. The effects of visceral fat on amyloid pathology were partially reduced in people with higher HDL.
“An important implication of our work is that managing Alzheimer’s risk in obesity will need to include addressing the related metabolic and lipid problems that often occur with higher body fat levels,” said senior study author Cyrus A. Raji, MD, Ph. D., associate professor of radiology at MIR.
Although previous studies have shown the role of high BMI in damaging brain cells, no comparable study has examined the differential role of visceral and subcutaneous fat or metabolic profile, especially in terms of Alzheimer’s amyloid pathology already in middle age, Dr. Dolatshahi pointed out.
“This study goes beyond using BMI to more accurately characterize body fat with MRI, revealing important insights into why obesity may increase the risk of Alzheimer’s disease,” said Dr. Dolatshahi.
Drs. Raji, Dolatshahi and colleagues also present a study at RSNA 2024 that shows how obesity and visceral fat reduce blood flow in the brain.
In that study, the researchers performed brain and abdominal MRI in cognitively normal middle-aged individuals with a wide range of BMI and compared whole-brain blood flow and regional cerebral brain MRI in individuals with high versus low visceral and subcutaneous fat. The high visceral fat group showed lower blood flow throughout the brain. No significant difference was observed in cerebral blood flow in the high versus low subcutaneous fat groups.
“This work will have a significant impact on public health, as nearly three in four Americans are overweight or obese,” said Dr. Raji. “Knowing that visceral obesity negatively impacts the brain opens the possibility that treatment with lifestyle changes or appropriate weight loss medications could improve cerebral blood flow and potentially reduce the burden and risk of Alzheimer’s disease. “
Other co-authors are Paul K. Commean, BEE, Mahshid Naghashzadeh, MS, Sara Hosseinzadeh Kassani, Ph.D., Jake Weeks, BS, Caitlyn Nguyen, BS, Abby McBee-Kemper, BS, Nancy Hantler, BS, LaKisha Lloyd , M.Sc., Shaney Flores, M.S., Yifei Xu, M.S., Jingxia Liu, Ph.D., Claude B. Sirlin, M.D., Bettina Mittendorfer, Ph.D., Joseph E. Ippolito, M.D., Ph.D., John C. Morris, M.D., and Tammie L.S. Benzinger, M.D., Ph.D. This research was awarded the RSNA Trainee Research Prize.